Efficacy of fimasartan/hydrochlorothiazide combination in hypertensive patients inadequately controlled by fimasartan monotherapy

Moo-Yong Rhee, Sang Hong Baek, Weon Kim, Chang Gyu Park, Seung Woo Park, Byung-Hee Oh, Sang-Hyun Kim, Jae-Joong Kim, Joon-Han Shin, Byung-Su Yoo, Se-Joong Rim, Jong-Won Ha, Joon Hyung Doh, Youngkeun Ahn, Jei Keon Chae, Jeong Bae Park, Soon-Kil Kim, Cheol Ho Kim, Moo-Yong Rhee, Sang Hong Baek, Weon Kim, Chang Gyu Park, Seung Woo Park, Byung-Hee Oh, Sang-Hyun Kim, Jae-Joong Kim, Joon-Han Shin, Byung-Su Yoo, Se-Joong Rim, Jong-Won Ha, Joon Hyung Doh, Youngkeun Ahn, Jei Keon Chae, Jeong Bae Park, Soon-Kil Kim, Cheol Ho Kim

Abstract

Background: The study reported here compared the blood pressure (BP)-lowering efficacy of fimasartan alone with that of fimasartan/hydrochlorothiazide (HCTZ) combination in patients whose BP goal was not achieved after 4 weeks of treatment with once-daily fimasartan 60 mg.

Methods: Patients with sitting diastolic blood pressure (siDBP) ≥90 mmHg with 4 weeks of once-daily fimasartan 60 mg were randomly assigned to receive either once-daily fimasartan 60 mg/HCTZ 12.5 mg or fimasartan 60 mg for 4 weeks. After 4 weeks, the dose was increased from fimasartan 60 mg/HCTZ 12.5 mg to fimasartan 120 mg/HCTZ 12.5 mg or from fimasartan 60 mg to fimasartan 120 mg if siDBP was ≥90 mmHg.

Results: Of the 263 randomized patients, 256 patients who had available efficacy data were analyzed. The fimasartan/HCTZ treatment group showed a greater reduction of siDBP compared to the fimasartan treatment group at Week 4 (6.88±8.10 mmHg vs 3.38±7.33, P=0.0008), and the effect persisted at Week 8 (8.67±9.39 mmHg vs 5.02±8.27 mmHg, P=0.0023). Reduction of sitting systolic BP in the fimasartan/HCTZ treatment group was also greater than that in the fimasartan treatment group (at Week 4, 10.50±13.76 mmHg vs 5.75±12.18 mmHg, P=0.0069 and, at Week 8, 13.45±15.15 mmHg vs 6.84±13.57 mmHg, P=0.0007). The proportion of patients who achieved a reduction of siDBP ≥10 mmHg from baseline and/or a mean siDBP <90 mmHg after 4 weeks of treatment was higher in the fimasartan/HCTZ treatment group than in the fimasartan treatment group (53.6% vs 39.8%, P=0.0359). The overall incidence of adverse drug reaction was 11.79% with no significant difference between the treatment groups.

Conclusion: The combination treatment of fimasartan and HCTZ achieved better BP control than fimasartan monotherapy, and had comparable safety and tolerance to fimasartan monotherapy.

Trial registration: ClinicalTrials.gov NCT01258673.

Keywords: angiotensin II type 1 receptor; angiotensin-converting enzyme inhibitor; angiotensin-receptor blocker; antihypertensive; blood pressure; renin–angiotensin–aldosterone system inhibitor.

Figures

Figure 1
Figure 1
Subject disposition and reasons for drop out. Abbreviation: HCTZ, hydrochlorothiazide.
Figure 2
Figure 2
(A) Response and (B) control rate of fimasartan/hydrochlorothiazide (HCTZ) and fimasartan at Weeks 4 and 8 from baseline.

References

    1. Turnbull F, Blood Pressure Lowering Treatment Trialists’ Collaboration Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet. 2003;362(9395):1527–1535.
    1. Kim TW, Yoo BW, Lee JK, et al. Synthesis and antihypertensive activity of pyrimidin-4(3H)-one derivatives as losartan analogue for new angiotensin II receptor type 1 (AT1) antagonists. Bioorg Med Chem Lett. 2012;22(4):1649–1654.
    1. Lee SE, Kim YJ, Lee HY, et al. Investigators Efficacy and tolerability of fimasartan, a new angiotensin receptor blocker, compared with losartan (50/100 mg): a 12-week, phase III, multicenter, prospective, randomized, double-blind, parallel-group, dose escalation clinical trial with an optional 12-week extension phase in adult Korean patients with mild-to-moderate hypertension. Clin Ther. 2012;34(3):552–568.
    1. Lee H, Kim KS, Chae SC, Jeong MH, Kim DS, Oh BH. Ambulatory blood pressure response to once-daily fimasartan: an 8-week, multicenter, randomized, double-blind, active-comparator, parallel-group study in Korean patients with mild to moderate essential hypertension. Clin Ther. 2013;35(9):1337–1349.
    1. Olives C, Myerson R, Mokdad AH, Murray CJ, Lim SS. Prevalence, awareness, treatment, and control of hypertension in United States counties, 2001–2009. PLoS One. 2013;8(4):e60308.
    1. Kim HJ, Kim Y, Cho Y, Jun B, Oh KW. Trends in the prevalence of major cardiovascular disease risk factors among Korean adults: results from the Korea National Health and Nutrition Examination Survey, 1998–2012. Int J Cardiol. 2014;174(1):64–72.
    1. Dahlöf B, Sever PS, Poulter NR, et al. ASCOT Investigators Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet. 2005;366(9489):895–906.
    1. Kochar M, Guthrie R, Triscari J, Kassler-Taub K, Reeves RA. Matrix study of irbesartan with hydrochlorothiazide in mild-to-moderate hypertension. Am J Hypertens. 1999;12(8 Pt 1):797–805.
    1. McGill JB, Reilly PA. Telmisartan plus hydrochlorothiazide versus telmisartan or hydrochlorothiazide monotherapy in patients with mild to moderate hypertension: a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. Clin Ther. 2001;23(6):833–850.
    1. Chrysant SG, Weber MA, Wang AC, Hinman DJ. Evaluation of antihypertensive therapy with the combination of olmesartan medoxomil and hydrochlorothiazide. Am J Hypertens. 2004;17(3):252–259.
    1. Hughes AD. How do thiazide and thiazide-like diuretics lower blood pressure? J Renin Angiotensin Aldosterone Syst. 2004;5(4):155–160.
    1. Coleman A, Freeman P, Steel S, Shennan A. Validation of the Omron 705IT (HEM-759-E) oscillometric blood pressure monitoring device according to the British Hypertension Society protocol. Blood Press Monit. 2006;11(1):27–32.
    1. Gleim GW, Rubino J, Zhang H, et al. A multicenter, randomized, double-blind, parallel-group trial of the antihypertensive efficacy and tolerability of a combination of once-daily losartan 100 mg/hydrochlorothiazide 12.5 mg compared with losartan 100-mg monotherapy in the treatment of mild to severe essential hypertension. Clin Ther. 2006;28(10):1639–1648.
    1. Flack JM, Saunders E, Gradman A, et al. Study Group for Losartan in African Americans with Hypertension Antihypertensive efficacy and safety of losartan alone and in combination with hydrochlorothiazide in adult African Americans with mild to moderate hypertension. Clin Ther. 2001;23(8):1193–1208.
    1. Ruilope LM, Simpson RL, Toh J, Arcuri KE, Goldberg AI, Sweet CS. Controlled trial of losartan given concomitantly with different doses of hydrochlorothiazide in hypertensive patients. Blood Press. 1996;5(1):32–40.
    1. Sun NL, Zhu JR, Zhao Y, Tu YM, Co-Diovan Trial Investigators Combination antihypertensive therapy with valsartan and hydrochlorothiazide in Chinese patients with mild-to-moderate hypertension. Curr Med Res Opin. 2008;24(10):2863–2871.
    1. Bönner G, Multicentre Study Group Antihypertensive efficacy and tolerability of candesartan-hydrochlorothiazide 32/12.5 mg and 32/25 mg in patients not optimally controlled with candesartan monotherapy. Blood Press Suppl. 2008;2:22–30.
    1. Campbell M, Sonkodi S, Soucek M, Wiecek A. A candesartan cilexetil/hydrochlorothiazide combination tablet provides effective blood pressure control in hypertensive patients inadequately controlled on monotherapy. Clin Exp Hypertens. 2001;23(4):345–355.
    1. Sachse A, Verboom CN, Jäger B. Efficacy of eprosartan in combination with HCTZ in patients with essential hypertension. J Hum Hypertens. 2002;16(3):169–176.
    1. MacKay JH, Arcuri KE, Goldberg AI, Snapinn SM, Sweet CS. Losartan and low-dose hydrochlorothiazide in patients with essential hypertension. A double-blind, placebo-controlled trial of concomitant administration compared with individual components. Arch Intern Med. 1996;156(3):278–285.
    1. Benz JR, Black HR, Graff A, Reed A, Fitzsimmons S, Shi Y. Valsartan and hydrochlorothiazide in patients with essential hypertension. A multiple dose, double-blind, placebo controlled trial comparing combination therapy with monotherapy. J Hum Hypertens. 1998;12(12):861–866.
    1. Mallion JM, Carretta R, Trenkwalder P, et al. Co-Diovan Study Group Valsartan/hydrochlorothiazide is effective in hypertensive patients inadequately controlled by valsartan monotherapy. Blood Press Suppl. 2003;1:36–43.
    1. Lee H, Yang HM, Lee HY, et al. Efficacy and tolerability of once-daily oral fimasartan 20 to 240 mg/d in Korean Patients with hypertension: findings from Two Phase II, randomized, double-blind, placebo-controlled studies. Clin Ther. 2012;34(6):1273–1289.
    1. Morgan DB, Davidson C. Hypokalaemia and diuretics: an analysis of publications. Br Med J. 1980;280(6218):905–908.
    1. Black HR. The evolution of low-dose diuretic therapy: the lessons from clinical trials. Am J Med. 1996;101(3A):47S–52S.
    1. Kasiske BL, Ma JZ, Kalil RS, Louis TA. Effects of antihypertensive therapy on serum lipids. Ann Intern Med. 1995;122(2):133–141.

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